Synthesis and Evaluations of GLP-1 Secretion and Anti-Diabetic Effect in KKAy Mice of New Tricyclic Compounds
摘要:
Glucagon-like peptide-1 (GLP-1), which belongs to the family of incretins, plays important role for the regulation of plasma glucose. Accordingly, GLP-1-based therapies for type 2 diabetes have recognized as one of the most interesting target. In this study, we have found the new tricyclic compounds having strong GLP-1 secretion from human intestinal L cells, and anti-diabetic properties in spontaneously obese and diabetic KKAy mice. The most potent compound 5ka was obtained as the unexpected product, and we would like to report the details of the synthesis, structure elucidations, pharmacological activities on secretion of GLP-1, and anti-diabetic effects using diabetic KKAy mice.
[EN] MODULATORS OF EXCHANGE PROTEINS DIRECTLY ACTIVATED BY CAMP (EPACS)<br/>[FR] MODULATEURS DE PROTÉINES D'ÉCHANGE DIRECTEMENT ACTIVÉES PAR L'AMPC (EPAC)
申请人:UNIV TEXAS
公开号:WO2013119931A1
公开(公告)日:2013-08-15
Embodiments of the invention are directed to compounds that inhibit an activity of EP AC proteins and methods of using the same. The inventors have developed a sensitive and robust high throughput screening (HTS) assay for the purpose of identifying EPAC specific inhibitors (Tsalkova et al. (2012) PLOS ONE 7(1 ):e30441).
该发明的实施例涉及抑制EPAC蛋白活性的化合物以及使用这些化合物的方法。发明人已经开发了一种敏感且稳健的高通量筛选(HTS)测定方法,用于识别EPAC特异性抑制剂(Tsalkova等人(2012年)PLOS ONE 7(1):e30441)。
Nitriles in Heterocyclic Synthesis. Novel Synthesis of Pyridazine Derivatives
The crotononitriles 1a–c coupled with arenediazonium salts to yield either the acyclic mono- or dihydrazones depending on coupling reaction conditions. Both mono- and dihydrazones could be cyclized to the corresponding pyridazine derivatives. Direct formation of pyridazines on coupling 1b and 1c with arenediazonium salts was observed. Structures of reaction products are confirmed by spectral and analytical
Synthesis of 1,4,5-trisubstituted-1,2,3-triazoles via coupling reaction of diaminomaleonitrile with aromatic diazonium salts
作者:Amal Al-Azmi、Anita K. Kalarikkal
DOI:10.1016/j.tet.2013.11.003
日期:2013.12
3-triazol-4-yl)-2-iminoacetonitriles and 2-(5-amino-1-aryl-1H-1,2,3-triazol-4-yl)-2-oxoacetonitriles was achieved by the reaction of diaminomaleonitrile and phenyl/substituted phenyl diazonium chlorides. 4-Nitrophenyl diazonium chloride afforded 2-amino-3-(3-(4-nitrophenyl)triaz-1-en-1-yl)maleonitrile. Triazole iminoacetonitrile and maleonitrile derivatives were reacted further with excess acetone and benzaldehyde
制备2-(5-氨基-1-芳基-1 H -1,2,3-三唑-4-基)-2-亚氨基乙腈和2-(5-氨基-1-芳基-1)的温和方法通过二氨基马来腈与苯基/取代的苯基重氮氯化物的反应获得H -1,2,3-三唑-4-基)-2-氧代乙腈。4-硝基苯基重氮氯化物得到2-氨基-3-(3-(4-(硝基苯基)三唑-1-en-1-基)马来腈。三唑iminoacetonitrile和马来腈衍生物与过量的丙酮和苯甲醛进一步反应用1,8-二氮杂双环[5.4.0]十一碳-7-烯的催化量以得到5 -(5-亚氨基甲基-2,2-二甲基-2, 5-二氢恶唑-4-基)-3-芳基-3 H -1,2,3-三唑-4-胺和(E)-N-亚苄基-5-(5-亚氨基-2-芳基-2,5-二氢恶唑-4-基)-3-芳基-3 H -1,2,3-三唑-4-胺。当三唑氧乙腈和马来腈衍生物与乙酸羟胺在乙酸钠存在下反应时,观察到两个竞争反应,即亲核取代和亲核加成。
REACTIONS WITH HYDRAZONOYL HALIDES. PART 27<sup>[1]</sup>: SYNTHESIS OF SOME NEW TRIAZOLO[4,3-<i>a</i>]BENZIMIDAZOLE AND UNSYMMETRICAL AZINE DERIVATIVES
作者:Abdou O. Abdelhamid、Hussien F. Zohdi、M. M. M. Sallam、Nagla A. Ahmed
DOI:10.1080/10426500008045244
日期:2000.1
Abstract Triazolo[4,3-a]benzimidazole, unsymmetrical azine containing pyrazole moiety were synthesised via reactions of C-pyrazolôyl-N-p-chlorophenylhydrazonoyl bromide with each 2-(methylthio)benzimidazole and carbodithioates, respectively. Newly synthesised compounds were confirmed on the basis of elemental analysis, spectral data, and alternative route whenever possible.
Synthesis of 1-Arylazo-3-acetyl-1H-cinnolin-4-one Derivatives
作者:Mohamed S. Abbady、Abd El-Aal M. Gaber
DOI:10.1135/cccc19921149
日期:——
The biological activity of azocinnoline derivatives especially in the chemotherapy of Trypanosomiasis was already reported. Considering the foregoing and in continuation of our previous work, 3-acetyl-1H-cinnolin-4-one (I) has been well exploited as a coupling component.